Systemic Lupus Erythematous (SLE) is a disease characterized clinically by multi-organ system involvement and immunologically by the presence of serum autoantibodies which, by themselves and as immune complexes, cause organ system dysfunction. Recent studies in normal mice and humans show that antibody synthesis by bone marrow-derived (B) lymphocytes is a highly modulated process controlled by genetic factors and regulated by the interaction with thymus-derived (T) lymphocytes and monocytes. We propose studies based on the hypothesis that an abnormal regulation of antibody synthesis is a fundamental defect predisposing to SLE. Modulating effects of mononuclear cell subpopulations, corticosteroids and disease activity will be studied on three aspects of antibody synthesis. First, study of regulating factors affecting immunoglobulin synthesis (Ig) in SLE will be investigated using the in vitro pokeweed mitogen induced Ig synthesis assay system. Secondly, the control of specific anti-tetanus synthesis will be studied in vivo and in vitro following tetanus toxoid immunization. Thirdly, the control of autoantibody (anti-DNA) synthesis will be studied both in vivo and in vitro. These studies should determine: a) if there is an abnormality in the regulation of antibody synthesis in SLE; b) if this aberrance is general or antigen specific; and c) if the dysregulation predisposes to SLE or if it is a result of disease activity or therapy.